네이처 컨텐츠

Editorials

Rare rewards p.249

A catalogue of genetic information from some 60,000 people reveals unexpected surprises — and highlights the need to make genomic data publicly accessible to aid studies of rare diseases.

doi: 10.1038/536249a

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News

News Features

News & Views

Sixty years of living polymers p.276

In the 1950s, the discovery of a class of 'living' polymerization reaction revolutionized the field of polymer science by providing a way of controlling the molecular-weight distribution of polymers. The effects reverberate to this day.

Gary Patterson

doi: 10.1038/536276a

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A deep dive into genetic variation p.277

The exome is the portion of the genome that encodes proteins. Aggregation of 60,706 human exome sequences from 14 studies provides in-depth insight into genetic variation in humans. See Article p.285

Jay Shendure

doi: 10.1038/536277a

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Flipping the sleep switch p.278

Inactivation of a group of sleep-promoting neurons through dopamine signalling can cause acute or chronic wakefulness in flies, depending on changes in two different potassium-channel proteins. See Letter p.333

Stephane Dissel & Paul J. Shaw

doi: 10.1038/nature18918

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Elusive active site in focus p.280

The identification of the active site of an iron-containing catalyst raises hopes of designing practically useful catalysts for the room-temperature conversion of methane to methanol, a potential fuel for vehicles. See Letter p.317

Jay A. Labinger

doi: 10.1038/536280a

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Mechanics drives cell differentiation p.281

Several hypotheses have been formulated to explain how cells make the first lineage decision during mammalian embryonic development. An overarching mechanism now unifies these disparate models. See Letter p.344

Berenika Plusa & Anna-Katerina Hadjantonakis

doi: 10.1038/nature18920

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Superconducting electrons go missing p.282

'Overdoped' high-temperature superconductors, which have a high density of charge carriers, were thought to be well understood. An experiment challenges what we know about quantum physics in such systems. See Letter p.309

Jan Zaanen

doi: 10.1038/536282a

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Articles

Analysis of protein-coding genetic variation in 60,706 humans OPEN p.285

Exome sequencing data from 60,706 people of diverse geographic ancestry is presented, providing insight into genetic variation across populations, and illuminating the relationship between DNA variants and human disease.

Monkol Lek, Konrad J. Karczewski, Eric V. Minikel, Kaitlin E. Samocha, Eric Banks, Timothy Fennell, Anne H. O’Donnell-Luria, James S. Ware, Andrew J. Hill, Beryl B. Cummings + et al.

doi: 10.1038/nature19057

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Circadian neuron feedback controls the Drosophila sleep–activity profile p.292

A subset of dorsal clock neurons are identified in Drosophila as sleep-promoting cells, which participate in a feedback loop with pacemaker neurons to drive both midday siesta and night-time sleep.

Fang Guo, Junwei Yu, Hyung Jae Jung, Katharine C. Abruzzi, Weifei Luo, Leslie C. Griffith & Michael Rosbash

doi: 10.1038/nature19097

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Defining the clonal dynamics leading to mouse skin tumour initiation p.298

Skin stem cells, but not their progenitors, are able to form tumours owing to the ability of oncogene-targeted stem cells to increase symmetric self-renewing division and a higher p53-dependent resistance to apoptosis.

Adriana Sánchez-Danés, Edouard Hannezo, Jean-Christophe Larsimont, Mélanie Liagre, Khalil Kass Youssef, Benjamin D. Simons & Cédric Blanpain

doi: 10.1038/nature19069

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Letters

High-efficiency two-dimensional Ruddlesden–Popper perovskite solar cells p.312

Thin-film solar cells were fabricated using layered two-dimensional perovskites with near-single-crystalline out-of-plane alignment, which facilitates efficient charge transport leading to greatly improved power conversion efficiency with technologically relevant stability to light exposure, humidity and heat stress.

Hsinhan Tsai, Wanyi Nie, Jean-Christophe Blancon, Constantinos C. Stoumpos, Reza Asadpour, Boris Harutyunyan, Amanda J. Neukirch, Rafael Verduzco, Jared J. Crochet, Sergei Tretiak + et al.

doi: 10.1038/nature18306

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The active site of low-temperature methane hydroxylation in iron-containing zeolites p.317

Iron-containing zeolites have an exceptional ability to convert methane into methanol, but their active site have been hard to study; now, magnetic circular dichroism has been used to explore the reactive species, providing a technique that should be generally applicable, and revealing the value of constraining active sites within a lattice to improve catalyst functionality.

Benjamin E. R. Snyder, Pieter Vanelderen, Max L. Bols, Simon D. Hallaert, Lars H. Böttger, Liviu Ungur, Kristine Pierloot, Robert A. Schoonheydt, Bert F. Sels & Edward I. Solomon

doi: 10.1038/nature19059

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Metallaphotoredox-catalysed sp3sp3 cross-coupling of carboxylic acids with alkyl halides p.322

In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research. However, the construction of a bond between two sp3-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions. In comparison to related procedures with sp2-hybridized species, the development of methods for sp3sp3 bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as β-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition. To address this issue, nickel-catalysed cross-coupling processes can be used to form sp3sp3 bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pre-generated organozinc, Grignard and organoborane species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step- and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp3sp3 coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp3sp3 bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox protocol is suitable for many primary and secondary carboxylic acids. The merit of this coupling strategy is illustrated by the synthesis of the pharmaceutical tirofiban in four steps from commercially available starting materials.

Craig P. Johnston, Russell T. Smith, Simon Allmendinger & David W. C. MacMillan

doi: 10.1038/nature19056

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An early geodynamo driven by exsolution of mantle components from Earth’s core p.326

Experiments show that magnesium oxide can dissolve in core-forming metallic melts at very high temperatures; core formation models suggest that a giant impact during Earth’s accretion could have contributed large amounts of magnesium to the early core, the subsequent exsolution of which would have generated enough gravitational energy to power an early geodynamo and produce an ancient magnetic field.

James Badro, Julien Siebert & Francis Nimmo

doi: 10.1038/nature18594

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Operation of a homeostatic sleep switch p.333

Sleep-promoting neurons in Drosophila are shown to switch between electrical activity and silence as a function of sleep need; the switch is operated by dopamine and involves the antagonistic regulation of two potassium channels.

Diogo Pimentel, Jeffrey M. Donlea, Clifford B. Talbot, Seoho M. Song, Alexander J. F. Thurston & Gero Miesenböck

doi: 10.1038/nature19055

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A human neurodevelopmental model for Williams syndrome p.338

A human neurodevelopmental model fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

Thanathom Chailangkarn, Cleber A. Trujillo, Beatriz C. Freitas, Branka Hrvoj-Mihic, Roberto H. Herai, Diana X. Yu, Timothy T. Brown, Maria C. Marchetto, Cedric Bardy, Lauren McHenry + et al.

doi: 10.1038/nature19067

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Structure of mammalian respiratory complex I p.354

Electron cryomicroscopy structures are provided for all core and supernumerary protein subunits of mammalian complex I, a 45-subunit enzyme that powers eukaryotic respiration.

Jiapeng Zhu, Kutti R. Vinothkumar & Judy Hirst

doi: 10.1038/nature19095

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